Advertisement
Original article| Volume 55, ISSUE 6, P403-411, December 1996

The induction of apoptosis in human cervical carcinoma (HeLa) cells by gamma-linolenic acid

      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      A high concentration (50 μg/ml) of gamma-linolenic acid (GLA) induced morphological lesions typical of apoptosis, as well as DNA fragmentation, in HeLa cells. A lower concentration of GLA (20 μg/ml), caused an increased proliferating cell nuclear antigen (PCNA) labelling, with 92.7% cells positive, compared to 27.7% at a concentration of 50 μg/ml GLA. In correlation with these results, the number of cells with degraded DNA below the Math Eq peak increased significantly in the 50 μg/ml GLA-treated cells, but increased only slightly in cells exposed to the lower level of GLA. The high levels of PCNA induced by 20 μg/ml GLA, in both G1 and S phases, may indicate a state of DNA repair synthesis, whilst at the higher concentration of GLA, most of the cells became apoptotic. Since apoptosis is associated with the deregulation of c-Myc expression, and as the Raf-1-MAP kinase cascade activates the expression of c-Myc and c-Jun, we investigated the effects of 20 and 50 μg/ml GLA on the Raf-1, c-Myc and c-Jun levels, and on the activity of MAP kinase. The results showed that 50 μg/ml GLA lowered the activity of MAP kinase. As expected with the decreased MAP kinase activity in the cells exposed to the higher level GLA, the c-Jun levels were also lowered. The levels of c-Myc, however, were increased. It is therefore possible that the deregulated expression of c-Myc in the HeLa cells exposed to the high level of GLA (50 μg/ml) may contribute to the induction of apoptosis in HeLa cells.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Prostaglandins, Leukotrienes and Essential Fatty Acids
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • De Kock M
        • Seegers J.C
        • Els H.J
        Effects of gamma-linolenic acid on mitosis and nuclear morphology in osteogenic sarcoma cells.
        S Afr Med J. 1992; 81: 467-472
        • De Kock M
        • Lottering M.-L
        • Seegers J.C
        Differential effects of gamma-linolenic acid on MG-63 and HeLa cells.
        Prostaglandins Leukot Essent Fatty Acids. 1994; 51: 109-120
        • Umansky S.R
        Apoptotic process in the radiation-induced death of lymphocytes.
        in: Tomei L.D Cope F.O Apoptosis: the molecular basis of cell death. 1st edn. Cold Spring Harbor Laboratory Press, New York1991: 193
        • Jayadev S
        • Linardic C.M
        • Hannun Y.A
        Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor α.
        J Biol Chem. 1994; 269: 5757-5763
        • Obeid L.M
        • Hannun Y.A
        Ceramide: a stress signal and mediator of growth suppression and apoptosis.
        J Cell Biochem. 1995; 58: 191-198
        • McConkey D.J
        • Orrenius S
        Cellular signaling in thymocyte apoptosis.
        in: Tomei L.D Cope F.O Apoptosis: the molecular basis of cell death. 1st edn. Cold Spring Harbor Laboratory Press, New York1991: 227
        • Amati B
        • Brooks M.W
        • Levy N
        • Littlewood T.D
        • Evan G.I
        • Land H
        Oncogenic activity of the c-Myc protein requires dimerization with Max.
        Cell. 1993; 72: 233-245
        • Seegers J.C
        • Böhmer L.H
        • Kruger M.C
        • Lottering M.-L
        • De Kock M
        A comparative study of ochratoxin A-induced apoptosis in Hamster Kidney and HeLa cells.
        Toxicol Appl Pharmacol. 1994; 129: 1-11
        • Bravo R
        • Frank R
        • Blundell P.A
        • MacDonald-Bravo H
        Cyclin/PCNA is the auxilliary protein of DNA-polymerase-δ.
        Nature. 1987; 326: 515-517
        • Burgering B.M.T
        • Bos J.L
        Regulation of Ras-mediated signalling: more than one way to skin a cat.
        TIBS. 1995; 20: 18-22
        • Nias A.H.W
        • Fox M
        Synchronization of mammalian cells with respect to the mitotic cycle.
        Cell Tissue Kinet. 1971; 4: 375-398
        • Lottering M.-L
        • Haag M
        • Seegers J.C
        Effects of 17β-estradiol metabolites on cell cycle events in MCF-7 cells.
        Cancer Res. 1992; 52: 5926-5932
        • Leist M
        • Gartner F
        • Bohlinger I
        • Tiegs G
        • Wendel A
        Application of the cell death detection ELISA for the detection of tumor necrosis factor-induced DNA fragmentation in murine models of inflammatory organ failure.
        Biochemica. 1994; 3: 18-20
        • Desantis L
        • Mangili F
        • Sassi I
        • Dirocco M
        • Cantaboni A
        Flow cytometric analysis of c-myc oncoprotein in non-small-cell lung carcinoma: Comparison with immunohistochemical results.
        Anal Cell Pathol. 1995; 8: 247-257
        • Lowry O.H
        • Rosebrough N.J
        • Farr A.L
        • Randall R.J
        Protein measurement with the folin phenol reagent.
        J Biol Chem. 1951; 193: 265-275
        • Clark-Lewis I
        • Sanghera J.S
        • Pelech S.L
        Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis-activated myelin basic protein kinase.
        J Biol Chem. 1991; 266: 15180-15184
        • Sommerville L
        • Wang K
        The ultrasensitive silver protein stain also detects nanograms of nucleic acids.
        Biochem Biophys Res Commun. 1981; 102: 52-58
        • Ochs R.L
        • Lischwe M.A
        • O'Leary P
        • Busch H
        Localization of nucleolar phosphoproteins B23 and C23 during mitosis.
        Exp Cell Res. 1983; 152: 260-265
        • Seegers J.C
        • Ochs R.L
        • Joubert W.S
        The effect of harmine on the localization of the nucleolar proteins C23 and B23.
        Eur J Cell Biol. 1985; 37: 213-215
        • Sancar A
        Mechanisms of DNA excision repair.
        Science. 1994; 266: 1954-1956
        • Li R
        • Waga S
        • Hannon G.J
        • Beach D
        • Stillman B
        Differential effects by p21 CDK inhibitor on PCNA-dependent DNA-replication and repair.
        Nature. 1994; 371: 535-537
        • Elledge S.J
        • Harper J.W
        Cdk inhibitors: on the threshold of checkpoints and development.
        Curr Opin Cell Biol. 1994; 6: 847-852
        • Harrington E.A
        • Fanidi A
        • Evan G.I
        Oncogenes and cell death.
        Curr Opin Genet Dev. 1994; 4: 120-129